Résumé en anglais

Objectifs: Patients with idiopathic hypersomnia never feel fully alert despite a normal or long sleep night. The spectrum of the symptoms is insufficiently studied.

Methods: We interviewed 62 consecutive patients with idiopathic hypersomnia (with a mean sleep latency lower than 8 min or a sleep time longer than 11 h) and 50 healthy controls using a questionnaire on sleep, awakening, sleepiness, alertness and cognitive, psychological and functional problems during daily life conditions.

Results: Patients slept 3 h more on weekends, holidays and in the sleep unit than on working days. In the morning, the patients needed somebody to wake them, or to be stressed, while routine, light, alarm clocks and motivation were inefficient. Three-quarters of the patients did not feel refreshed after short naps. During the daytime, their alertness was modulated by the same external conditions as controls, but they felt more sedated in darkness, in a quiet environment, when listening to music or conversation. Being hyperactive helped them more than controls to resist sleepiness. They were more frequently evening-type and more alert in the evening than in the morning. The patients were able to focus only for 1 h (versus 4 h in the controls). They complained of attention and memory deficit. Half of them had problems regulating their body temperature and were near-sighted.

Conclusions: Mental fatigability, dependence on other people for awakening them, and a reduced benefit from usually alerting conditions (except being hyperactive or stressed) seem to be more specific of the daily problems of patients with idiopathic hypersomnia than daytime sleepiness.

Article complet

INTRODUCTION

Idiopathic hypersomnia is characterized by chronic, daily excessive daytime sleepiness despite normal sleep. The diagnosis is difficult, as more common causes of sleepiness, including sleep deprivation, the use of drugs or substances, psychiatric or medical disorders and genuine sleep disorders (sleep disordered breathing, narcolepsy and periodic leg movement disorders) had to be first ruled out. Since it has been distinguished from narcolepsy (Roth, 1957), idiopathic hypersomnia has been defined according to small series of cases with various clinical forms. Alertness is continuously decreased during the daytime, possibly culminating in the irresistible need for sleeping. Naps are either refreshing or, more typically, long and unrefreshing (American Academy of Sleep Medicine, 2005). Patients may also report a prolonged difficulty waking up with automatic behaviour, confusion and repeated returns to sleep, a symptom named sleep drunkenness. Several clinical forms have been described in the past, including patients with sleepiness alone (monosymptomatic) and patients with a prolonged night of sleep and sleep drunkenness upon awaking (polysymptomatic; Roth, 1981).

Idiopathic hypersomnia is now divided into hypersomnia with and without a long (>10 h) sleep time (American Academy of Sleep Medicine., 2005). Hypersomnia is idiopathic when the symptoms and polygraphic findings cannot be better explained by medical or psychiatric (mostly depression) disorders. Based on these evolving definitions, several series of patients have been published (Aldrich, 1996; Anderson et al., 2007; Baker et al., 1986; Billiard et al., 1998; Bove et al., 1994; Bruck and Parkes, 1996; Coleman et al., 1982; Komada et al., 2005; Roth et al., 1972; Sforza et al., 2000; Vernet and Arnulf, 2009; Vgontzas et al., 2000); they contain 10–77 patients. These series suggest that idiopathic hypersomnia is a rare disease, representing 8:10 to 1:10 patients with narcolepsy, with a prevalence of approximately 0.005% (Billiard and Dauvilliers, 2001). Most patients are young at disease onset. This is usually a life-long disease, although recent series suggest that hypersomnia may spontaneously disappear in 14–25% of patients (Anderson et al., 2007; Billiard, 1996; Bruck and Parkes, 1996).

These limited case series mainly evaluate the night-time sleep and the narcolepsy-associated features (sleepiness, hallucina- tions and sleep paralysis) but, more rarely, some problems associated with the autonomic nervous system, such as Raynaud-like syndrome, migraine and orthostatic syncope (Bassetti and Aldrich, 1997; Matsunaga, 1987; Roth, 1981; Roth et al., 1972). They frequently lack healthy controls, as idiopathic hypersomnia is usually compared with narcolepsy. The spectrum of problems linked to idiopathic hypersomnia, however, is much larger in clinical practice and daily life. For example, there are a lack of data on how long patients with hypersomnia usually sleep when working (versus during the weekend or on holidays), what is their most efficacious means to wake up, how their alertness changes with environmental (types of light, sounds and company) factors, how long they can focus, and the numerous daytime problems they can experience. In our experience, many patients with idiopathic hypersomnia complain of fatigue rather than of sleepiness, and have difficulties completing the classical Epworth sleepiness score, suggesting that their complaint is not exactly (or simply) sleepiness. We took the opportunity of a large prospective cohort of patients with idiopathic hypersomnia studied over 4 years and systematically interviewed the patients on their subjective symptoms using a formal questionnaire.

MATERIALS AND METHODS

Subjects

Between 2005 and 2008, all patients being monitored for 48 h on the suspicion of idiopathic hypersomnia completed a face-to-face interview and a standardized questionnaire. The patients who completed the whole questionnaire and later received a final diagnosis of idiopathic hypersomnia by an experienced sleep neurologist were included in this study. The patients with idiopathic hypersomnia met the following inclusion criteria: (1) complaints of excessive daytime sleepiness occurring daily for at least 3 months; (2) no improvement of sleepiness with an increase of the night-time length for 15 days (excluding the diagnosis of behaviourally induced insufficient sleep syndrome); (3) a mean sleep latency (MSL) during multiple sleep latency tests (MSLT) lower than 8 min; or (4) a total sleep time >11 h on long-term (24 h) sleep monitoring following a habituation night (Vernet and Arnulf, 2009).

We excluded the patients with: (1) sleep-disordered breathing, defined by a respiratory disturbance index greater than 10 events /h (this index included apnoea, hypopnoea and respiratory effort-related arousal events, with the flow limitation being measured with a nasal cannula); (2) narcolepsy defined as the presence of a definite cataplexy or MSL lower than 8 min and multiple sleep-onset rapid eye movement (REM) periods during the MSLT; (3) hypersomnia because of a medical or psychiatric condition (e.g. Parkinson's disease, hypothyroidism, genetic disease or depression); (4) hypersomnia because of a drug or substance and (5) circadian sleep disorders. In addition, the patients with a REM sleep latency lower than 20 min during the night-time or during the daytime monitoring (at more than one nap) were excluded, as they may be a form of atypical narcolepsy.Thus, 62 patients (43 women, of whom nine were postmenopausal and 19 men) were included in the study.

Fifty paid subjects volunteered to take part as controls after recruitment by advertisement and selection by the physician. They were matched by age and sex with the patients. The subjects were selected after a medical interview and had no complaints regarding their sleep, no excessive daytime sleepiness (defined as the absence of spontaneous or elicited complaint, and also having a score on the Epworth sleepiness scale lower than 10), no chronic sleep deprivation (determined using a questionnaire on sleep habits), no shift or night work, no severe medical illness and no use of medications known to modify sleep and wakefulness. Thus, 50 healthy subjects (27 women, of whom 6 were postmenopausal and 23 men) completed the study. In addition, 30 of these 50 controls completed a 48-h sleep monitoring. All subjects signed an informed consent to take part. The local ethics committee accepted the protocol.

Investigations

A large, systematic questionnaire was developed after interviewing sleep neurologists experienced in treating narcolepsy and hypersomnia (I. Arnulf., S. Leu, M. A. Buzare and M. Minz), and prospectively interviewing a panel of 30 patients with idiopathic hypersomnia already diagnosed in the sleep disorders unit. New participants underwent a face-to-face interview about classical sleep symptoms (cataplexy, sleep drunkenness, sleep paralysis and restorative naps) and com- pleted the sleep questionnaire. This auto-questionnaire contained five sections (Appendix S1). The sleep section included questions on the sleep duration at the time of the study and when the subject was 10-years old (as we wanted to determine if sleep excess was permanent or developed with time), the usual sleep times of the parents, the self-estimated sleep time need and naps (refreshing type, duration and frequency). In the section on morning and post-nap awakening, the subjects evaluated their difficulties on waking up and looked at the effects on awakening of a series of stimuli (e.g. alarm clock, light) or events (e.g. scheduled appointment). The section on circadian variation of daytime sleepiness and fatigue across the daytime included the morningness–eveningness questionnaire (Horne and Ostberg, 1976), and questions such as "what is your level of alertness?" for five times of the day, or "at what time of the day are you the most tired and the most awake?". The section on sleepiness and alertness contained the Epworth sleepiness scale (Johns, 1991), the Pichot fatigue scale (Pichot and Brun, 1984) and the Fatigue Severity Score (Krupp et al., 1989) and evaluated the fluctuation of sleepiness and alertness in the presence of environmental conditions or stimuli (light, sounds) or internal stimuli (sports, motivation). The section on non-sleep problems included memory, automatic behaviours, ability to focus, the hospital anxiety and depression (HAD) rating scale (Zigmond and Snaith, 1983) and somatic com- plaints. Each section contained mostly multiple-choice ques- tions and some open, more descriptive questions, in order to catch more adequately the exact complaints of the patients.

The sleep- and wake-monitoring procedures included:

(1) a habituation night with sleep and respiratory monitoring from 11:00 to 06:30 hours; followed the next day by (2) five standard MSLT at 08:00, 10:00, 12:00, 14:00 and 16:00 hours that were terminated after 20 min if no sleep occurred and after 15 min asleep if sleep occurred (Carskadon et al., 1986); and followed the next evening by (3) a long-term (24 h) sleep monitoring.

All of the patients were monitored, while 30 ⁄ 50 (60%) of the healthy controls underwent the full 48-h sleep-monitoring procedure.

Statistical analyses

After having checked the Gaussian distribution of the variables, we analysed the between-groups dichotomous variables using a chi-square test and analysed our continuous variables using an analysis of variance (Statistica 7.1, Stat Soft, Tulsa, OK, USA). A P-value less than 0.01 was considered to be significant (with corrections for repeated measures). The values are presented as mean ± SD (unless otherwise specified).

RESULTS

There were 62 patients with idiopathic hypersomnia and 50 controls. The sleep measures in both groups are displayed in Table S1. Among the patients with idiopathic hypersomnia, 25 (40%) had a long night-time sleep time (>10 h) and 37 (60%) had a normal night-time sleep time. As many patients as controls regularly practice a sport. The 30 controls who underwent the sleep monitoring were not different with respect to demography and answers to the sleep questionnaires from the 20 controls who did not (data not shown). The disease occurred when 21.2 ± 13.0 years old. Before the disease onset, 23% of the patients had insomnia and 38% had a major change in sleep habits. Half of the patients reported an important personal event before the disease onset (death of a loved one, divorce, pneumopathy, end of military service or end of a high level of sport practice).

Usual sleep duration during the night and during naps

Patients and controls rarely had one parent (at least) who sleeps more than 9.5 h (12.5% versus 5.1%, P = 0.40). Their usual sleep times as a child, and during work days, weekends and holidays, are indicated in Fig. 1. The patients and controls slept the same amount of time when they were 10- years old. While the patients slept as long as controls during the working days, they slept much longer during the weekend and holidays. As a result, they extended their usual sleep by +3.00 ± 2.21 h on the weekend and holidays, versus +1.12 ± 1.22 h in the controls (P < 0.001). Their maximum time asleep per night (range 10–20 h of sleep in patients versus 10–13 h in controls, P < 0.001) and their self- estimated necessary sleep time were also longer than in the controls. The time asleep during holidays was greater than the sleep needs in both the patients (P = 0.009) and the controls (P = 0.002). Almost all (90%) of the patients reported to sometimes sleep longer than 10 h consecutively, versus 27% of controls. The patients slept more than 10 h consecutively for a mean of 7.4 ± 7.2 nights ⁄ month versus 0.9 ± 1.9 nights ⁄ months in the controls (P < 0.0001). The total sleep time measured in the sleep lab during the continuous 24-h-long monitoring was similar in both groups to the usual sleep time declared during the weekend or the holidays (P < 0.001). As for naps, their frequency (2.7 ± 2.6 per week in patients versus 1.5 ± 1.9 per week in controls, P = 0.01), average duration (1.21 ± 0.51 h in patients versus 0.50 ± 0.49 h in controls, P = 0.018) and maximum duration (2.47 ± 1.45 h in patients versus 1.11 ± 0.50 h in controls, P < 0.001) were higher in patients than in controls.

Waking up

In the hypersomnia group, there were less patients feeling refreshed after a usual night than in the control group (Table 1). The patients felt as hungry on awakening as controls, as 58% of the patients felt a normal or great hunger for breakfast, versus 78% of the controls (P = 0.03). As many as 78% of patients had difficulties waking up in the morning and could not sometimes hear the alarm clock, a much larger percentage than in the controls. Difficulties with waking up were associated with more frequent automatic behaviours (P = 0.006). To specifically study the sleep drunkenness, we isolated the patients with frank, genuine sleep drunkenness (i.e. need three alarm clocks to wake up, need to put the alarm clock on a stack of plates or need to be pulled out of the bed by parents and remaining sleepiness for at least 1 h and having this symptom almost every day). There were 18 patients in this case. We contrasted them with the other extreme of the group, i.e. the 32 patients with an easy time waking up (Table S2). We removed from the analysis the patients "in-between", i.e. with unclear difficulties in waking up (i.e. mild sleep inertia, able to wake up, but mildly groggy for 1 h).

The 18 patients with genuine sleep drunkenness had a total sleep time similar to the 32 patients with no sleep drunkenness at all, a similar sleep efficacy and fragmentation. They had a period of slow-wave sleep after 06:00 hours as often as the others. In contrast, the patients with sleep drunkenness tended to be more frequently of the evening type, as indicated by a lower Horne–Ostberg score (41.0 ± 12.6 versus 52.6 ± 12.3, P = 0.02). The other scores or measures were not different.

For the question "What helps you with waking up?", the presence of a human (not an animal) helping the subject to wake up and the stress of being late were more helpful for obtaining a full awakening in the patients than in the controls (Fig. 2). The alarm clock, motivation, sounds, a new activity and hunger or thirst were chosen as often in the two groups, but a bright light and habit helped less frequently in the patients than the controls. Some patients changed the tone and music of their alarm every other day, so that they would not get used to it, or tried an alarm clock set for a hearing- impaired person, with a vibrating pillow, or coupled their alarm clock to a distributor that vapourized cold water onto the face, but none of these helped. A patient used his stereo (set at a very high volume) as an alarm, which was located in a far corner of the room, combined with obstacles on the floor, so that he would need to stand up, walk, avoid the obstacles and then shut-off the sound. He would manage to wake up with this system.

An almost similar pattern was found in patients after daytime naps, with two-thirds of them having difficulties waking from naps versus one-third of the controls. Of interest, short naps were not felt to be as refreshing in 75% of the hypersomniacs (while two-thirds of controls felt them to be refreshing). The patients with short refreshing naps had shorter usual sleep times (9.36 ± 1.33 h versus 11.49 ± 2.40 h, P = 0.003). As for long naps, the perception of not being refreshed afterwards was similar in both groups (48% versus 35%). Eventually, as many as 56% of the hypersomniacs reported the occasional, urgent need to lie down, while this symptom was exceptional (9%) in the controls.

Circadian fluctuations of alertness

The Horne–Ostberg score was lower in patients (48.3 ± 12.3) than in controls (56.7 ± 9.1, P < 0.001), indicating that more patients than controls were evening type. Fig. 3 displays how patients and controls scored on a five-point scale for alertness ⁄ tiredness. The patients always scored lower than the controls, but their changes throughout the day (better alertness at 11:00 hours and 18:00 hours, lower at 13:00 hours) paralleled those of the controls. However, when they were asked to designate the clock time when they felt the most tired, it was at the time of awakening in 85% of the patients (versus 48% of the controls, P=0.003) and, in contrast, the time was at 22:00 hours in 83% of the controls versus 41% of the hypersomniacs (P < 0.001).

Daytime alertness

During the MSLT, the patients had lower sleep onset latencies than the controls, whatever the time test. As expected, the score on the Epworth sleepiness scale was higher in the 62 patients than in the 50 controls (15.9 ± 3.9 versus 6.5 ± 3.1, P < 0.001). Similarly, when daytime functioning was expressed in terms of fatigue, the severity of fatigue was scored as higher in the patients than in the controls, whether on the fatigue severity scale (49.7 ± 11.2 versus 32.7 ± 11.2, P < 0.001) or on the Pichot fatigue scale (25.9 ± 7.9 versus 12.0 ± 4.6, P < 0.001). Most patients were able to differentiate sleepiness from tiredness. The first one was described as an ability (and a need) to fall asleep soon and could be alleviated with modafinil. In contrast, tiredness was not necessarily associated with a need and an ability to sleep (and sometimes even with an inability to fall asleep), but was expressed as a "cognitive fatigue" or "loss of vital energy" (not physical). A patient reported: "I feel sleepy only once a day (after lunch), but I feel tired all the time". Another patient said: "modafinil is like Botox", it keeps my eyes open, but my brain is still asleep". We then duplicated all questions below using first the terms sleepy ⁄ awake and then the terms tired ⁄ alert, but we obtained similar answers, regardless of the pair of adjectives that was used.

The conditions considered as equally sedative in both groups were "waiting ⁄ being bored" and routine condition. A quiet activity was felt as sedative in 64% of the patients versus 16% in the controls (P < 0.001). Unexpectedly, the need to focus on a task (whether manual or intellectual) was felt as sedative by more (29%) patients than controls (7%, P = 0.006). The conditions able to fight sleepiness (drinking caffeine, being stressed, performing a sport, being active or hyperactive, doing something really interesting, thinking too much and being hungry or thirsty) were reported as often by the patients and the controls. Stress was considered as the most alerting condition in the controls (chosen by 73% of them). Being hyperactive was the most alerting condition in the patients (chosen by 65% of them). Some patients reported that they would be more attentive if they were standing up rather thansitting, and they would learn or rehearse their class easier while walking. A patient wrote down lists of consecutive, useless numbers on a notebook while attending a meeting so that she felt more attentive. Another would draw or fill a cross-word while waiting for the train and travelling. Several patients spoke continuously, with a rapid flow, especially when tired.

We tested the effects of various environmental stimuli on the ability to adequately function during the daytime (Fig. 4). As for the lighting conditions, darkness had a much more sedative effect in the patients than in the controls, while both groups felt a similar benefit when exposed to the sun light and an unchanged (halogen neon or incandescent light, rainy day) or decreased (flashing light) alertness when exposed to the other various types of lights. In contrast, the sound conditions, such as a quiet environment, music or listening passively to other people, were clearly alerting in controls but not in hypersomniacs. A loud environment was tiring and sedative in both groups. Being on holidays and watching a nice landscape were stimulants in both groups, but slightly less so in the patients than in the controls. Stress, workload and frustration had similar tiring effects in both groups. As for interactions with other people, being with friends was a stimulant in both groups, but more so in the controls than in the hypersomniacs. Being alone or with strangers did not change the level of alertness in the controls but decreased it slightly, but significantly, in the hypersomniacs.

Cognitive, psychological and somatic problems

The patients reported attention deficit more frequently than the controls (Table 2). They felt able to focus for only 1 h in a row versus almost 4 h in controls. As many as 70% of them had difficulties focusing on their task in a loud environment versus 38% of controls (P=0.03). A young student with idiopathic hypersomnia noticed: "When I must rehearse and learn by heart my lessons, I cannot stand my girlfriend speaking to me, or any background sound". Patients reported more frequent memory problems, forgot something more often (an appointment, a thing to do) and lost their belongings more frequently. Automatic behaviours and being lost in thought were reported in the patients as often as in the controls. But mind going blank, not remembering the beginning of an activity, telling something inappropriate in a conversation and a significant inappropriate life mistake were more frequent in the patients than in the controls (Table 2). Examples of automatic behaviours included putting one's cell phone in the fridge, bringing the garbage bag to the dentist appointment instead of leaving it in the garage, putting clothes in the dishwasher, using a hairbrush to wash one's teeth, putting one's glasses in a videotape case (and not finding them for 3 months) and forgetting to pick up the children at school. As for psychological aspects, the patients as a group scored higher both on the anxiety and depression scales (Table 2). The frequency of subjects with a score higher than the threshold of 11 (suggesting either an anxiety disorder or depression) was similar in both groups.

As for somatic complaints, more patients than controls experienced problems in regulating their body temperature (heavy sweating, feeling colder or, on the contrary, warmer, than the other people in the same room) and cold extremities (Table 2). One-third of them would occasionally faint versus 9% of the controls. Similarly, about one-fifth of the patients had digestive problems or palpitations, while it was rare in the controls. Half of the patients were short-sighted (and wore glasses) versus only 23% of the controls. The other eye problems (astigmatism, far-sightedness and needing sun- glasses) were similarly frequent in both groups. Headache, tinnitus and losing one's hair were equally frequent in both groups (data not shown). One-third of the patients reported an allergy versus only 14% in the controls.

DISCUSSION

In this controlled study of the subjective sleep and alertness in idiopathic hypersomnia, patients have a night-time sleep time as short as controls during the working days, but much longer during the weekend, holidays and in the sleep laboratory. As many as 78% of patients could hardly wake up in the morning or from a daytime nap, with no specific benefit of alarm clocks, bright light, motivation, routine and sounds, except if somebody wakes them up or if they are stressed. Daytime naps are more frequent and longer than in the controls. Short naps are refreshing in the controls, but not in 75% of the patients. During the daytime, the alertness is modulated by the same external conditions (e.g. higher during a sunny day than a grey day) in the controls and in the patients, but the patients feel more sedated in darkness, in a quiet environment, when listening to music or a conversation, when alone or not. Being hyperactive, helps them to resist sleepiness more than the controls. In contrast to the controls, the patients are more evening time and more alert in the evening than in the morning.The patients are able to focus only for 1 h (versus almost four consecutive hours in controls). They complain of attention and memory deficit, with frequently mislaid objects. Half of them complain of cold extremities and are near-sighted.

Sleep excess

The Greek-origin word "hypersomnia" means "excess of sleep", which captures one of the main essences of the disease. One may regret that the word hypersomnia has progressively changed meaning to designate many conditions associated with excessive daytime sleepiness, but not with a real excess of sleep (Billiard, 1994). In idiopathic hypersomnia, the sleep excess is best expressed in unrestricted conditions, such as during the weekend, on holidays and in the sleep laboratory, with an average of three additional hours slept. One may notice in this study that the sleep time obtained during long-term monitoring in the sleep laboratory is very similar to the usual sleep time during holidays and on weekends in the patients, suggesting it is not a completely artificial measure, disconnected from true life. Controls also sleep longer in these conditions, only an extra hour here, but even more in epidemiological surveys (http:// www.sleepfoundation.org, poll 2006). Hypersomniacs and controls sleep less during the working days, suggesting that an actimetry, or a sleep agenda, in these forced life conditions is poorly sensitive, except if one pays attention to large sleep differences between working days (more than 7 h) and weekend days (more than 10–12 h). In addition, the sleep debt caused by the constraint of working is probably much higher in hypersomniacs. Controls can sleep a maximum of 10–13 h in a row (versus 10–20 h in hypersomniacs), suggesting that being able to sleep occasionally more than 13 h in a row (without previous sleep debt) is specific to hypersomniacs. Notably, the patients and the controls reported the same amount of sleep when they were 10 years old and the same frequency of a "long-sleeper" phenotype in one or both parents. These results suggest that the disease is acquired and does not result from an additional sleep load on an already "sleepy" phenotype.

Sleep drunkenness

Sleep drunkenness is another symptom of hypersomnia and constitutes an important disability in the daily life of the patients. Seventy-eight percent of the patients had difficulties with morning awakening, and one-third had sleep drunkenness, paralleling the percentages (21 and 52%) reported in other series (Anderson et al., 2007; Billiard and Dauvilliers, 2001). However, this last symptom is highly specific, as clear-cut sleep drunkenness is not found in controls. Compared with hypersomniacs without any sleep drunkenness, those with sleep drunkenness are more frequently evening types on the Horne–Ostberg score. In this article, hypersomniacs are more frequently evening types than controls, and more alert in the evening than in the morning. These data suggest that they have a delayed shift in their circadian rhythm and a longer circadian period. To support this hypothesis, one had to perform a continuous measure of the body core temperature and the melatonin secretion (ideally during a constant routine to avoid the masking effect of a long sleep on the temperature) in these two groups. In our series, the patients with sleep drunkenness did not have a longer sleep time. The fact that sleep drunkenness is not correlated with sleep duration argues against an extreme form of sleep inertia (a normal period of hypovigilance and impaired cognitive and behavioural performances following awakening from naps, increasing with the duration of the earlier sleep in healthy subjects). The same observation can be made for naps, as not only long but also short naps (which had to limit the sleep inertia) are felt as non- refreshing by 75% of hypersomniacs. Eventually, one may imagine that forced awakening during slow-wave sleep at the end of the night would promote disorientation, diminished mentation and blunted responses to questions. In our study, however, slow-wave sleep is equally frequent at the end of the night in the patients with and without sleep drunkenness, suggesting that the presence of late slow-wave sleep is not causing the sleep drunkenness. However, this conclusion is limited by the fact that we do not inquire about sleep drunkenness the very morning of night 2, but as a general, frequent symptom. Notably, Roth et al. (1972) observed that sleep drunkenness is infrequent in the settings of the sleep laboratory, possibly as a consequence of a lighter, more fragmented sleep before awakening. The methods that make awakening in the morning easier are different in the patients and controls. Of interest, the habit of waking up at a certain time and the presence of a bright, sunny light are quite efficient in the controls but not in the hypersomniacs. The regulation of sleep termination has been thought to be embedded in a daily circadian rhythm (Czeisler et al., 1980), controlling in parallel the release of pituitary and adrenal hormones. A routine, predicted time of sleep offset is preceded by a gradual increase of adrenocorticotrophin 90–180 min before the final awakening (Born et al., 1999). Whether hypersomniacs have delayed pituitary hormone secretion in the morning (with a cortisol phase delay as observed by Nevsimalova et al., 2000 in 15 hypersomniacs) or have become resistant to these strong internal circadian signals is partly unknown. In this study, the intervention of someone helps them to wake up, but makes them quite dependent on others. Notably, a human voice calling someone by his first name is better processed by the sleeping brain than a sound during non-REM and REM sleep (Bastuji et al., 2002). A subject can not only call but also touch and even shake the sleeping hypersomniac, leading to a multimodal arousal. As a practical consequence, one may advise hypersomniacs to live in a student community or with a family (a parent or a caregiver) with someone responsible for waking them up.

Daytime alertness

Although patients insist on differentiating between sleepiness (as estimated by their ability to fall asleep in passive conditions, e.g. using the MSLT or the Epworth score) and tiredness ⁄ decreased alertness, we could not find stimuli that preferentially affect the sleepiness rather than the tiredness ⁄ alertness, they always go in the same direction. Billiard (1994) previously noticed that most patients with idiopathic hypersomnia never feel fully awake during the daytime, even if they can resist sleep easier than narcoleptics (Komada et al., 2005). During the daytime, alertness is modulated by the same external conditions (e.g. higher during a sunny day than a grey or rainy day or than when exposed to artificial lighting, regardless of whether it is neon, halogen or incandescent lighting) in the controls and patients, but the patients feel more sedated than the controls in darkness. Bright light (e.g. 8– 10 000 lux, closer to sunlight) has already been demonstrated to increase alertness in workers (Santhi et al., 2008), but we are not aware of studies showing an alertness change reported during a grey or rainy day, so one may encourage hypersomniacs to use sun-like bright lights when working. Noises and loud environments are perceived as sedative by the controls and hypersomniacs, possibly because of the increase load to focus ones attention. In contrast, a quiet environment, music and conversation help the controls (but not the hypersomniacs) to feel alert and focused. However, being with friends (and not with strangers) is perceived as stimulating in the hypersomniacs, even if it is to a lesser degree than the controls. Taken together, it seems that hypersomnia narrows the spectrum of conditions associated with full alertness, given that the patients feel tired in the presence of over-stimulating conditions (a loud environment, strangers and flashing light), and feel sleepy in under-stimulating conditions (darkness, left alone or listening to a conversation). Basically, it appears in this study that the patients would feel all right only during holidays, in a nice landscape with sun and friends. One may wonder if they use, in this case, the motivation ⁄ mood system to stay awake rather than the usual arousal systems. In addition, being hyperactive helps hypersomniacs to resist sleepiness more than controls. They use this term to describe both any increased motor activity (such as standing up rather than sitting, walking while learning or speaking continuously) and doing several tasks at the same time (such as writing while listening). Hyperactivity is a symptom of attention deficit ⁄ hyperactivity disorder. In this case, excessive motor activity can be viewed as a strategy to stay awake and alert, while decreased attention could be the consequence of the hypoarousal (Lecendreux et al., 2000). We suspect that the hypersomniacs use the motor arousal to supplement their cognitive arousal, and the stress of multi-tasks to increase their level of alertness by fighting monotony. As a consequence, they could get more tired. Hence, we wonder if the feeling of tiredness that the patients described as different from sleepiness is a general lack of mental energy, as a consequence of using multi-modal systems to fight sleepiness.

Cognitive and somatic symptoms

A deficit of attention has been previously described in patients with idiopathic hypersomnia (Oosterloo et al., 2006). Executive dysfunction is a consequence of many disorders with excessive daytime sleepiness, including narcolepsy, sleep apnoea syndrome and sleep deprivation (Anderson et al., 2009; Lis et al., 2008; Naumann et al., 2006); it had to be improved using stimulants. We could not find any previous report of defective memory in idiopathic hypersomnia. Whether the patients have a long-term memory deficit (i.e. in absence of attention and working memory deficit) is unlikely, but had to be formally assessed. In the present study, the patients notably reported that they could not sustain attention for more than 1 h, versus almost 4 h in the controls. This limited mental endurance suggests that patients with idiopathic hypersomnia have a cognitive fatigability, as it was described in patients with chronic fatigue syndrome (Capuron et al., 2006); this aspect could be tested on sustained attention tests. Automatic behaviours are found both in patients and in controls, but the severity is different. Telling something inappropriate in a conversation and making a mistake during a usual activity are more frequently experienced by patients than by healthy controls (except if they are sleep deprived). Hence, one may interview patients about the frequency of these behaviours. When the patients mix two different activities during routine tasks, they seem only partly able to shift from an action (bringing the garbage to the cellar) to another action (going to the dentist). As this sort of shifting (and focusing) is seen as a frontal lobe function, it suggests that their automatic programs are no longer driven by the frontal lobe. Although they are not monitored, they do not seem to be drowsy or in stage one during these behaviours. Rather, they are unfocused. The automatic behaviours can be partly responsible for the "memory" problems reported by the patients. For example, a patient lost her glasses for 3 months because she had put them into a videotape case. She spontaneously reports this incident as a memory problem.

Some somatic problems regarding the autonomic nervous system (Raynaud-like syndrome, migraine and orthostatic syncope) have already been described in hypersomnia (Bassetti and Aldrich, 1997; Matsunaga, 1987; Roth et al., 1972). In this study, some functional equivalents (cold extremities and fainting) are indeed more frequent in hypersomniacs than in controls, while there is no more headache in the patient group. In addition, half of the hypersomniacs are near-sighted, 38% are allergic and 25% have problems regulating their temperature. The mechanism of these symptoms is unknown, they could contribute to the burden of the disease.

The symptoms reported in this article are subjective, which constitutes a limitation of this work. There is no formal testing of the cognitive status by a neuropsychologist, no measure of supine hypotension, no systematic sight assessment in the controls, so that a bias towards over-reporting in patients is still possible. The questionnaire is, however, the same for any subject, whether hypersomniac or not. On the contrary, we try to catch the somatic problems of the patients, which are by definition subjective.